Review
Biochemistry & Molecular Biology
Laura A. Huff, Shan Yan, Mark G. Clemens
Summary: Cells have evolved extensive signaling mechanisms to maintain redox homeostasis, with a critical role of oxidants in normal signaling. However, excessive oxidants can lead to elevated oxidative stress, causing alterations in cellular operations and damage to cellular components. The cellular response to oxidative stress includes redox sensors that regulate the DNA damage response and orchestrated changes to the epigenome, protecting and regulating the nuclear genome.
Review
Cell Biology
Yulia Mitiagin, Ari Barzilai
Summary: The review summarizes accumulating evidence that ataxia-telangiectasia mutated kinase is crucial for maintaining cellular homeostasis and has both nuclear and cytoplasmic functions. However, the specific functions of ataxia-telangiectasia mutated that lead to cerebellar degeneration when lost are still unknown. The review discusses the role of ataxia-telangiectasia mutated in cerebellar pathology, including its nuclear functions in DNA damage response circuits and its cytoplasmic and mitochondrial functions related to cellular homeostasis.
NEURAL REGENERATION RESEARCH
(2023)
Article
Allergy
Ismail Ogulur, Tugce Ertuzun, Burcu Kocamis, Yasemin Kendir Demirkol, Emel Uyar, Ayca Kiykim, Dilek Baser, Gozde Yesil, Hacer Akturk, Ayper Somer, Ahmet Ozen, Elif Karakoc-Aydiner, Meltem Muftuoglu, Safa Baris
Summary: Heterozygous relatives of ataxia-telangiectasia (AT) patients are at increased risk for certain AT-related manifestations, and parents of AT patients show an increase in infection frequency. It is hypothesized that parents may exhibit immune alterations similar to their affected children.
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2021)
Review
Cell Biology
Julio Aguado, Cecilia Gomez-Inclan, Hannah C. Leeson, Martin F. Lavin, Yosef Shiloh, Ernst J. Wolvetang
Summary: Ataxia-telangiectasia (A-T) is a complex disorder characterized by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. The premature aging component of A-T is of great importance in driving the disease.
AGEING RESEARCH REVIEWS
(2022)
Review
Health Care Sciences & Services
Sharon A. McGrath-Morrow, Cynthia C. Rothblum-Oviatt, Jennifer Wright, Haley Schlechter, Maureen A. Lefton-Greif, Valerie A. Natale, Thomas O. Crawford, Howard M. Lederman
Summary: Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive ataxia, oculocutaneous telangiectasias, and immune system impairment. Patients with A-T have an increased risk of malignancy, leading to premature death.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2021)
Article
Biochemistry & Molecular Biology
Sapir Schlam-Babayov, Ariel Bensimon, Michal Harel, Tamar Geiger, Ruedi Aebersold, Yael Ziv, Yosef Shiloh
Summary: This study conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells to reveal the fine-tuned dynamics and relationships between PIKKs in the response to genotoxic stress. The results highlight the complex interactions among ATM, ATR, and DNA-PK in the DDR.
Article
Biochemistry & Molecular Biology
Ji-Hoon Lee, Seung W. Ryu, Nicolette A. Ender, Tanya T. Paull
Summary: Loss of ATM kinase leads to neurodegeneration and protein aggregation, driven by PARPs associating with PAR-associated genomic sites, causing protein species to arise from intrinsically disordered proteins. Single-strand DNA breaks, dependent on reactive oxygen species, transcription, and R-loops, are implicated in this process. The phenomenon is also observed in Mre11 A-T-like disorder mutants, providing a hypothesis for protein integrity loss and cerebellum dysfunction in A-T.
Review
Genetics & Heredity
Motohiro Yamauchi
Summary: Chromosome rearrangements are structural variations in chromosomes and are associated with a variety of human diseases. Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by chromosome rearrangements at the cellular level, particularly in T lymphocytes. The defective gene in A-T is ataxia-telangiectasia mutated (ATM), which plays a central role in cellular response to DNA damage, including suppressing chromosome rearrangements.
Article
Biochemistry & Molecular Biology
Divya A. Shiroor, Kuang-Tse Wang, Bhargav D. Sanketi, Justin K. Tapper, Carolyn E. Adler
Summary: Stem cells acquire mutations during division, but can activate the DNA damage response network to repair or induce apoptosis. In planarian flatworms, ATM promotes radiation-induced apoptosis, which is important for long-term animal survival.
Article
Biochemistry & Molecular Biology
Sayanthooran Saravanabavan, Gopala K. Rangan
Summary: Increased DNA damage response signaling in kidney cyst-lining epithelial cells (CECs) may be a target for therapy in ADPKD. However, inhibiting ATM kinase and low-dose cisplatin together does not selectively induce cell death in CECs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Maria Likhatcheva, Roben G. Gieling, James A. L. Brown, Constantinos Demonacos, Kaye J. Williams
Summary: Genotoxic stress can activate the ATM kinase, with potential involvement of Suv39H1 and Tip60 in ATM activation under hypoxic conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Jun Wang, Holly R. Thomas, Zhang Li, Nan Cher (Florence) Yeo, Hannah E. Scott, Nghi Dang, Mohammed Iqbal Hossain, Shaida A. Andrabi, John M. Parant
Summary: Cellular stress can lead to human disease pathologies due to aberrant cell death. The study found both common and unique molecular pathways involved in different stress responses, with p53 and puma playing key roles. The data suggests that Puma may be the key mediator of p53-dependent apoptosis, and inhibitors targeting Puma could have therapeutic applications.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Goutham Narayanan Subramanian, Abrey Jie Yeo, Magtouf Hnaidi Gatei, David John Coman, Martin Francis Lavin
Summary: The ATM protein kinase has diverse functions in the cell, including protecting DNA, maintaining cellular homeostasis, and safeguarding against external and internal damage.
Article
Multidisciplinary Sciences
Heathcliff Dorado Garcia, Fabian Pusch, Yi Bei, Jennifer von Stebut, Glorymar Ibanez, Kristina Guillan, Koshi Imami, Dennis Guergen, Jana Rolff, Konstantin Helmsauer, Stephanie Meyer-Liesener, Natalie Timme, Victor Bardinet, Rocio Chamorro Gonzalez, Ian C. MacArthur, Celine Y. Chen, Joachim Schulz, Antje M. Wengner, Christian Furth, Birgit Lala, Angelika Eggert, Georg Seifert, Patrick Hundsoerfer, Marieluise Kirchner, Philipp Mertins, Matthias Selbach, Andrej Lissat, Frank Dubois, David Horst, Johannes H. Schulte, Simone Spuler, Daoqi You, Filemon Dela Cruz, Andrew L. Kung, Kerstin Haase, Michela DiVirgilio, Monika Scheer, Michael V. Ortiz, Anton G. Henssen
Summary: This study demonstrates that PAX3-FOXO1-expressing alveolar rhabdomyosarcoma (ARMS) cells are sensitive to ataxia telangiectasia and Rad3 related protein (ATR) inhibition. Inhibition of ATR leads to replication stress exacerbation and reduced DNA repair pathway activity, increasing the sensitivity of ARMS cells to PARP1 inhibition. Treatment with ATR and PARP1 inhibitors in combination induces complete regression of primary patient-derived ARMS xenografts, suggesting potential clinical applications. Additionally, the study identifies the RAS-MAPK pathway and FOS gene family as inducers of resistance to ATR inhibition in ARMS cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jakub Czarny, Marta Andrzejewska, Olga Zajac-Spychala, Elzbieta Latos-Grazynska, Agata Pastorczak, Kamila Wypyszczak, Aleksandra Szczawinska-Poplonyk, Izabela Niewiadomska-Wojnalowicz, Agnieszka Wziatek, Patrycja Marciniak-Stepak, Michal Dopierala, Jadwiga Maldyk, Katarzyna Jonczyk-Potoczna, Katarzyna Derwich
Summary: Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by DNA repair defect, chromosomal instability, and hypersensitivity to radiation. Successful clinical management of patients with AT is challenging due to poor treatment response, high toxicity, and the need to avoid radiation exposure. This case report describes a 7-year-old female patient with AT and LBCL with IRF4 rearrangement who achieved a favorable outcome through treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)